title: Uterine estrogen receptors are increased by RU486 in late pregnant rhesus macaques but not after spontaneous labor.
abstract: Progesterone withdrawal as a mechanism for parturition in primates is controversial. The progesterone antagonist RU486, given in late pregnancy to rhesus monkeys at a dose of 47 mmol/kg.day (20 mg/kg.day), causes an increase in uterine activity, but not the expected increase in amniotic fluid prostaglandins or cervical dilatation. We, therefore, studied the effect of RU486 on estrogen receptor (ER) localization and concentration in reproductive tract tissues in rhesus monkeys during late gestation and after spontaneous labor at term. Distribution of ER in pregnant uterine tissues was studied by immunocytochemical techniques and quantified by a biochemical assay, both of which employed a monoclonal antibody specific for ER. ER was not present in amnion and chorion by immunocytochemical investigation; however, a significant increase in receptor staining was seen in decidua and myometrium after RU486 treatment compared to that in both pregnant control tissues and parturient tissues. Sucrose gradient assay of nuclear (n) and cytosolic (c) ER revealed a low level of ER (expressed as fmol of estradiol bound/mg of DNA) in pregnant and parturient decidua (pregnant: nER = 7.3 +/- 2.4, cER = 17.1 +/- 6.4; parturient, nER = 7.7 +/- 3.1, cER = 16.4 +/- 8.8) and myometrium (pregnant: nER = 21.7 +/- 4.1, cER = 20.8 +/- 5.3; parturient: nER = 30.0 +/- 2.8, cER = 10.7 +/- 6.7). In contrast, tissues collected from RU486-treated animals contained high levels of ER in decidua (nER = 52.3 +/- 16.8, cER = 240.5 +/- 145.3) and myometrium (nER = 77.0 +/- 19.2; cER = 66.5 +/- 31.6). We conclude that 1) the increase in ER in decidua and myometrium after RU486 treatment is the result of a decrease in the inhibitory action of progesterone on ER and documents the progesterone receptor antagonism by RU486 during induced myometrial contractility in late pregnant rhesus monkeys; 2) the absence of ER from amnion and chorion indicates that the normally observed increase in prostaglandin production by rhesus fetal membranes during labor is not mediated by ER; and 3) the absence of a change in the concentration of ER in decidua and myometrium from pregnant control monkeys and those in spontaneous labor indicates that an increase in ER (and, by inference, a withdrawal of receptor-mediated progesterone inhibition) is not part of the normal events in preparation for parturition in primates.
authors.affiliation: Division of Reproductive Biology and Behavior, Oregon Regional Primate Research Center, Beaverton 97006.
authors.forename: G J
authors.initials: GJ
authors.lastname: Haluska
authors.forename: N B
authors.initials: NB
authors.lastname: West
authors.forename: M J
authors.initials: MJ
authors.lastname: Novy
authors.forename: R M
authors.initials: RM
authors.lastname: Brenner
mesh_terms: D000650:Amnion / Q000032:analysis; D000818:Animals; D002467:Cell Nucleus / Q000032:analysis; D002499:Centrifugation, Density Gradient; D002823:Chorion / Q000032:analysis; D003600:Cytosol / Q000032:analysis; D003656:Decidua / Q000032:analysis; D005321:Extraembryonic Membranes / Q000032:analysis; D005260:Female; D007150:Immunohistochemistry; D007743:Labor, Obstetric; D008253:Macaca mulatta; D015735:Mifepristone / Q000494:pharmacology*; D009215:Myometrium / Q000032:analysis; D011247:Pregnancy; D011960:Receptors, Estrogen / Q000032:analysis / Q000378:metabolism*; D015854:Up-Regulation; D014590:Uterine Contraction / Q000187:drug effects; D014599:Uterus / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*
chemical_list: D011960:Receptors, Estrogen; D015735:Mifepristone